2-hydrocarbyl aminovinyl phosphonates or phosphinates

ABSTRACT

Reagents particularly useful for the preparation of Alpha Beta -unsaturated aldehydes are provided herein, which reagents consist of compounds of the general formula: WHEREIN R1 is a lower alkyl group, R2 is a member selected from the group consisting of R1O, a lower alkyl group, an aralkyl group of seven to eight carbon atoms and an aryl group of six to seven carbon atoms, R3 is a member selected from the group consisting of an acyclic or cyclic alkyl group of one to six carbon atoms and an aryl group of six to seven carbon atoms, and R4 is a member selected from the group consisting of a hydrogen atom, a lower alkyl group, an aralkyl group of seven to eight carbon atoms, and a halogen atom. These compounds react with carbonyl compounds to form unsaturated aldehydes and are especially useful in the synthesis of various pharmaceutical compounds such as various steroids, vitamin A, vitamin D, etc.

United States Patent Nagata et al.

Z-HYDROCARBYL AMINOVINYL PHOSPHONATES OR PHOSPHINATES inventors: Wataru Nagata, Nishinomiya-shi; Yoshio Hayase, Sakai-shi, Osaka, both of Japan Assignee: Shionogi & Co., Ltd., Higashi-ku, Osaka,

Japan Filed: Feb. 27, 1969 Appl. No.: 803,106

Foreign Application Priority Data March 7, 1968 Japan ..43/14901 March 19, 1968 Japan ..43/18134 March 19, 1968 Japan... ....43ll8l35 March 30, 1968 Japan ..43/20805 Primary Examiner-Joseph Rebold Assistant Examiner-Anton H. Sutto Attorney-Wenderoth, Lind & Ponack [5 7] ABSTRACT Reagents particularly useful for the preparation of nip-unsaturated aldehydes are provided herein, which reagents consist of compounds of the general formula:

wherein R is a lower alkyl group, R is a member selected from the group consisting of R 0, a lower alkyl group, an antikyl group of seven to eight carbon atoms and an aryl group of six toseven carbon atoms, R is a member selected from the group consisting of an acyclic or cyclic alkyl group of one to six carbon atoms and an aryl group of six to seven carbon atoms, and R is a member selected from the group consisting of a hydrogen atom, a lower alkyl group, an aralkyl group of seven to eight carbon atoms, and a halogen atom. These compounds react with carbonyl compounds to form unsaturated aldehydes and are especially useful in the synthesis of various pharmaceutical compounds such as various steroids, vitamin A, vitamin D, etc.

15 lass ev ses Z-HYDROCARBYL AWOVINYL PHOSPI-IONATES R PHOSPWATES The present invention relates to novel reagents for aldehyde synthesis, to processes for the preparation thereof and to uses thereof.

More particularly, the present invention relates to novel reagents for fonnyl-olefination represented by the general formula:

wherein R is a lower alkyl group, R is a member selected from the group consisting of RO, a lower alkyl group, an aralkyl group of seven to eight carbon atoms and an aryl group of six to seven carbon atoms, R is a member selected from the group consisting an acyclic or cyclic alkyl group of one to six carbon atoms and an aryl group of six to seven carbon atoms, and R is a member selected from the group consisting of a hydrogen atom, a lower alkyl group, an aralkyl group of seven to eight carbon atoms, a lower alkoxycarbonyl group, and a halogen atom.

The methods for preparing a, fl-unsaturated aldehydes, socalled formyl-olefination, consisting of adding two carbon atoms to carbonyl functions as illustrated by the accompanying equation, have widely been utilized as useful synthetic method in chemical or pharmaceutical industries, particularly in preparations of pharrnaceutically useful compounds such as various steroids, vitamin A, vitamin D, carotenoids and other natural products or medicaments or intermediates thereof.

Representative of the methods is indirect one including modifications thereof, consisting of adding an acetylenic anion to a carbonyl compound followed by rearrangement to desired a,B-unsaturated aldehyde, for example, as illustrated by the following reaction sequence.

[G. Saucy et al., l-lelv. Chim. Acta, 42, 1952 (1959) However, these methods are disadvantageous in requirement of multi-step reactions or in low yield or in limitation of application.

Alternative most striking methods are so-called aldol-condensation consisting of condensing an active methylene group adjacent to an aldehyde group with another carbonyl group.

ln general, the various methods for reacting the compounds involving an active methylene group adjacent to the electron withdrawing group (e.g. nitro group, carbonyl group, sulfonyl group, a carboxylic acid ester, cyano group etc.) with other carbonyl compounds have been known as well as that of the active methylene group adjacent to aldehyde (aldol-condensation). However, these reactions are accompanied by sidereactions undesirable for the objective reaction in many cases, such as self-condensation or polymerization, since the reactions are usually carried out in the presence of a basic catalyst. In order to remove these side-reactions, various methods, for example, Mannich reaction, Darzen condensation, Reformat-. sky reaction, have been reported. However, the satisfactory process for fonnyl-olefination has been unknown.

On the contrary, the process for preparing olefins consisting of reacting a carbonyl compound with a phosphonium ylide (C6H5)3P=CHC0-CGH5 II 6Hs)tP= CHCO2C2Hs III (CqHs)sP=CH-CEN IV (Cslls)al=CIIClIO V example, as indicated in the following equation. Accordingly,

the reactivity of the reagents is remarkably low in comparison with the Wittig reagents involving no electron withdrawing group in the adjacent position. For example, the abovedescribed compound V reacts with benzaldehyde to yield cinnamic aldehyde, while not react with ketones. Furthermore, the compound V does no react with an aldehyde located at the sterically hindered position (e.g. an aldehyde located at the tertiary position) [Trippett and Walker, J. Chem. Soc., 1266 (1961) Wadsworth and his co-workers developed the reaction method using phosphonate carbanion as a modification of the Wittig reaction [J. Am. Chem. Soc.,- 83,1733 (1961) This reaction may be characterized by utilizing the phosphonate carbanion more reactive than the Wittig reagent in order to increase the reactivity of the active methylene compounds involving the electron withdrawing group in the adjacent position. For example, the reactivity of the reagents represented by the following formulae Vl IX, involving the electron withdrawing group in the adjacent position, could considerably be increased Therefore, in spite of these various attempts, the sufficient process for formyl-olefination has not yet been developed.

The present inventors had studied various methods in order to remove these disadvantages and it has been discovered that the enarnine-type phosphonate compounds represented by the above-described general formula I have been excellently effective as reactive agents for preparing a,B-unsaturated aldehyde by condensing aldehydes involving the active methylene group at the a-position with other carbonyl compounds. The reactive agents of the present invention may be applied to all sorts of carbonyl compounds including aldehydes and ketones and effectively show remarkable reactivity even to the hindered carbonyl compounds such as aldehydes located at the tertiary position. Furthermore, the method of the present invention is much more effective than the above-mentioned other methods in stability of the reagents in reaction medium, in casinos of the reaction procedure, in improvement of the yield or in stereospecificity.

Each substituent of the reagents represented by the abovementioned general formula I is more precisely indicated as follows: R represents a lower alkyl group such as methyl, ethyl, n-propyl, n-butyl or the like, R has the same meaning as RO or is a member selected from the group consisting of a lower alkyl group such as methyl, ethyl, n'propyl, n-butyl or the like, an aralkyl group of seven to eight carbon atoms such as benzyl, phenylethyl, tolubenzyl or the like, and an aryl group of six to seven carbon atoms such as phenyl, totyl or the like, R? is a member selected from the group consisting of an acyclic or cyclic alkyl group of one to six carbon atoms such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, s-pentyl, t-pentyl, n-hexyl, cyclopentyl, cyclohexyl or the like, and an aryl group of six to seven carbon atoms, and R is a member selected from the group consisting of a hydrogen atom, a lower alkyl group such as methyl, ethyl, npropyl, i-propyl, n-butyl, n-pentyl, n-hexyl or the like, an aralkyl group of seven to eight carbon atoms such as benzyl, phenylethyl, tolubenzyl or the like, a lower alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl or the like, and a halogen atom such as chlorine, bromine or iodine atom.

Representative of the reagents (I) of the present invention are:

Dimethylphosphonoacetaldehyde methylamine enamine,

Dimethylphosphonoacetaldehyde i-propylamine enamine,

Dimethylphosphonoacetaldehyde t-butylamine enamine,

Dimethylphosphonoacetaldehyde cyclohexylamine enamine,

Diethylphosphonoacetaldehyde methylamine enamine,

Diethylphosphonoacetaldehyde i-propylamine enamine,

Diethylphosophonoacetaldehyde t-butylamine enamine,

Diethylphosphonoacetaldehyde cyclohexylamine enamine,

Diethylphosphonoacetaldehyde aniline enamine,

Di-n-propylphosphonoacetaldehyde t-butylamine enamine,

Di-n-propylphosphonoacetaldehyde cyclohexylamine enamine, Z-Dimethylphosphonopropionaldehyde t-butylamine enamine,

2-Dimethylphosphonopropionaldehyde cyclohexylamine enamine,

Z-Diethylphosphonopropionaldehyde t-butylamine enamine,

2-Diethylphosphonopropionaldehyde cyclohexylamine enamine,

Z-Diethylphosphono-n-butyraldehyde t-butylamine enamine,

t-butylamine Z-Diethylphosphono-2-bromoacetaldehyde cyclohexylamine enamine,

2-Diethylphosphono-2-chloroacetaldehyde t-butylamine enamine,

Ethyl-Z-cyclohexylaminovinyl phenylphosphinate,

Ethyl-l-methyl-Z-cyclohexylaminovinyl phenylphosphinate,

Ethyl-l-ethyl-2cyclohexylaminovinyl phenylphosphinate,

Ethyl-( l-benzyl-2-cyclohexylamino )vinyl phenylphos phinate,

Ethyl-2-t-butylaminovinyl phenylphosphinate,

Ethyl-( l-methyl-2-t-butylamino)vinyl phenylphosphinate,

Ethyl-( l-benzyl-2-t-butylamino)vinyl phenylphosphinate,

Ethyl-Z-t-butylaminovinyl ethylphosphinate, and

Ethyl-Z-cyclohexylarhino ethylphosphinate.

The reagents (I) of the present invention may be prepared from the compounds of the general formula X as illustrated by the following reaction sequence,

Ib (R"=R but a hydrogen atom in I) wherein R, R R and R each has the same meanings as described above.

The compounds (X) in the above-described reaction sequence may be prepared according to the known method as follows:

O CzHs wherein R and R each has the same meanings as described above, the acetal derivative of a-bromoacetaldehyde of the general formula XII is subjected to reaction with the phosphite derivative of the general formula XI and then the acetal protecting group of the resulting phosphonate or phosphinate derivative (XIII) is removed to the compound (X).

The reagents (Ia: R=H in I) can be prepared by reacting the compounds (X) with the primary amines represented by the general formula R Nl-I in a suitable solvent (e.g. methanol, ethanol, n-propanol, t-butanol, benzene, toluene, tetrahydrofuran etc.) or without any solvent at a temperature ranging from 0 C. to C. The reaction may be carried out according to the process for preparing so-called Schiff-base or the process for enamine formation.

The reagents (l'b: R =R but a hydrogen atom in I) can be prepared by further reacting the compounds (Ia) with the compounds, capable of releasing the radical R represented by the general formula R X in the presence of a catalyst.

The compounds of the general formula R X are alkyl halogenides consisting of an alkyl group such as methyl, ethyl, n-propyl, i-propyl, n-butyl, n-pentyl, n-hexyl or the like and a halogen atom such as chlorine, bromine or iodine atom (e.g. methyl iodide, ethyl bromide, n-butyl iodide, n-hexyl bromide etc.), aralkyl halogenides consisting of an aralkyl group such as benzyl, phenylethyl, tolubenzyl or the like and a halogen atom (e.g. benzyl chloride, phenylethyl bromide, tolubenzyl iodide etc.), lowe alkoxycarbonyl halides such as methyl chloroformate, ethyl chloroformate or the like, and halogenating agents. The halogenating agents in this process mean the reagents producing the positively charged halogen atom in the reaction medium, for example, chlorine (C12), bromine (Br iodine (l cyanogen bromide, cyanogen iodide, N- bromoacetamide (NBA), N-bromosuccinimide (NBS), N- chlorosuccinimide (NCS), N-chloro-p-toluenesulfonarnide (chloramine-T), N-chlorobenzenesulfonamide (chloramine- B), t-butyl hypochlorite, pyridinium bromide perbromide and the like.

The reaction of the compounds (Ia) with the compounds R X is usually carried out in a suitable inert solvent in the presence of a catalyst under cooling or at room temperature (about 30 40 C.), if necessary, under heating (such as refluxing temperature). The catalysts used in the reaction are, for example, lithium, sodium, lithium hydride, sodium hydride, sodium amide, potassium amide, Grignard reagents such as ethylmagnesium bromide, methylmagnesium iodide, ethylmagnesium chloride and the like, and organo metal compounds such as butyl lithium, phenyl lithium and the like. The preferred solvents are ethers such as diethyl ether,

'tetrahydrofuran, l,2-dirnethoxyethane, diglyme and the like,

and hydrocarbon solvents such as benzene, toluene, xylene and the like.

The resulting reagents (I) of the present invention may be applied to preparation of a,B-unsatt1rated aldehydes (XIV) increasing two carbon atoms from carbonyl compounds as illustrated by the following reaction sequence:

is usually carried out in an aprotic solvent in the presence of a basic catalyst. The usual reaction procedure may be indicated as follows: the reagent represented by the general formula (I) is dissolved in an aprotic solvent with a basic catalyst to form the anion represented by the following general formula:

R O O R R wherein R, R, R and R each has the same meanings as described above, and then the starting carbonyl compound is added to this solution. However, the reaction is not always carried out according to such successive procedure. For ex- XIV ample, the reaction may also be carried out by adding the basic catalyst into the previously prepared solution of the starting carbonyl compound and the reagent (1) in an aprotic solvent.

The basic catalysts used are metal alcoholate such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium t-butoxide, sodium t-butoxide and the like, sodium amide, potassium amide, lithium diethylamide, sodium hydride, lithium hydride, lithium triphenylmethide, methyl lithium, butyl lithium or Grignard reagents such as methylmagnesium bromide, ethylmagnesium bromide and the like.

Aprotic solvents, i.e. the solvent releasing no proton, are, for example, ethers such as diethyl ether, tetrahydrofuran, LZ-dimethoxyethane and the like, hydrocarbon solvents such as benzene, toluene, xylene and the like, N,N-dimethylformamide and the like.

The reaction temperature may be set according to the reactivity of the carbonyl compounds applied and the reaction may be carried out at room temperature or under cooling or sometimes under heating. Moreover, the reaction is preferably carried out under an inert gas such as nitrogen or argon, because of the reaction in the presence of a strongly basic catalyst. Furthermore, the reaction is preferably carried out under stirring in order to efiectively proceed the reaction.

The products obtained in the above-described process are the Schiff-bases involving the partial structure represented by the general formula XV,

wherein R and R each has the same meanings as described lated and purified according to the usual isolation and purification procedure used in the general synthetic chemistry, for example, extraction, distillation, recrystallization, column chromatography, thin layer chromatography, gas chromatography, or the methods by so-called carbonyl reagenm (e.g. Girard reagents, hydrazone, semicarbazone, oxime etc.

The invention will be better explained by the following examples which are not intended as a limitation thereof.

Diethylphosphonoacetaldehyde Cyclohexylamine Enamine To a solution of 30.2 g of diethylphosphonoacetaldehyde in ml of anhydrous methanol, there is added 19.2 ml of purified cyclohexylamine in nitrogen atmosphere under ice-cooling and stirring. The reaction mixture is kept at room temperature for 10 minutes under stirring and then the solvent is distilled off under reduced pressure. The residue is dissolved in ml of anhydrous ether, dried over anhydrous potassium carbonate, and then evaporated under reduced pressure. The resulting residue is purified by highly vacuum distillation in the presence of mg of potassium carbonate to afford 33.06 g of diethylphosphonoacetaldehyde cyclohexylamine enamine (74.4 percent yield) having bp. 151 152 C./o.04 mm Hg. The purity of this substance is confirmed by gas chrop y- Am 241 mp.(A 16,300). IR: .33;

3255, 1633 (shoulder), 1620, 1211, 1058, 1035, 955 cm'k' NMR: 6(CC1 1.25 (triplet), 3.25 (multiplet), 3.85 (multiplet), 6.7 (multiplet) ppm. Anal. Calcd. for C, H ,O NP: C, 55.15; H, 9.26; N, 5.36; P, 11.86. Found: C, 54.54; H, 9.55; N, 5.43; P, 12.03.

- diethylphosphonopropionaldehyde and ethyl-(1-benzyl-2-cyclohexylamino)vinyl -7 EXAMPLE 2 According to the same procedure as Example 1, dimethylphosphonoacetaldehyde t-butylarnine enamine, diethylphosphonoacetaldehyde t-butylamine enamine, ethyl- 2-cyclohexylaminovinyl phenylphosphinate, and ethyl-2-t-butylaminovinyl ethylphosphinate are prepared, respectively.

EXAMPLE 3 2-Diethylphosphonopropionaldehyde Enamine To a solution of 10.0 g of diethylphosphonoacetaldehyde cyclohexylamine enamine in 30 ml of anhydrous tetrahydrofuran, there is added dropwise 22.0 ml of ethylmagnesium bromide-tetrahydrofuran solution (2.31 mM/ml) within a period of 20 minutes under ice-cooling and stirring. After stirring for 40 minutes at room temperature, a solution of 8.10 g of methyl iodide in 10 ml of anhydrous tetrahydrofuran is added dropwise and then the reaction mixture is refluxed for 1.5 hours. After cooling, the reaction mixture is poured into icewater, extracted with dichloromethane-ether (1 3), washed with saturated sodium chloride aqueous solution and then evaporated under reduced pressure to yield 7.09 g of residue, which on crystallization from ether-pentane affords 7.00 g of 2-diethylphosphonopropionaldehyde cyclohexylamine enamine (66.6 percent yield) having mp. 61 64 C./73 C. (double melting point). UV: )t f' 246 my. (e 24,200). IR:

g 3265, 1642, 1221, 1057, 1031, 951 cm". Anal. C5158". for C H O NP: C, 56.71; H, 9.52; N, 5.09; P, 11.25. Found: C, 56.52; H, 9.59; N, 5.25; P, 11.20.

EXAMPLE 4 2-Diethylphosphono-3-phenylpropionaldehyde ylamine Enamine To a solution of 2.85 g of diethylphosphonoacetaldehyde cyclohexylamine enamine in 10.0 ml of anhydrous tetrahydrofuran, there is added dropwise 6.86 ml of 2.39N ethylmagnesium bromide-tetrahydrofuran solution within a period of 10 minutes under ice-cooling and stirring. After stirring for 1 hour under ice-cooling, a solution of 1.38 g of benzyl chloride in 4.0 ml of anhydrous tetrahydrofuran is added dropwise within a period of 5 minutes and then the reaction mixture is refluxed for 22 hours. After cooling, the reaction mixture is poured into ice-water, extracted with ether, washed with water, dried over anhydrous sodium sulfate and then evaporated to dryness to yield 3.09 g of residue, which on crystallization from ether-pentane affords 2.72 g of phenylpropionaldehyde cyclohexylamine enamine (71.2 percent yield) having mp. 79 82 C. UV: M 246.5 my. (6 15,960).1R: .gg;. 3406, 1636, 1603, 1235, 1057, 1031, 950 cm". Anal, Calcd. for c,,H .,,o,NP= C, 64.93; H, 8.61; N, 3.99; P, 8.82. Found: C, 65.35; H, 8.92; N, 4.04; P, 9.16.

Cyclohexylamine Cyclohex- EXAMPLE 5 According to the same procedure as Examples 3 and 4, 2-

t-butylamine enamine, ethyl-1-methyl-2-cyclohexylaminovinyl phenylphosphinate,

phenylphosphinate are prepared, respectively.

EXAMPLE 6 Acid , cyclohexylarnine enamine at the same temperature. The reaction mixture is poured into ice-water, extracted with ether, washed with water, dried over anhydrous sodium sulfate and then evaporated to dryness to yield 4.37 g of residue, which on purification by highly vacuum distillation affords 4.12 g of 2-diethylphosphono-3- (N-cyclohexyl)aminoacrylic acid ethyl ester (80.4 percent yield) having bp. 147 C./0.002 0.003 mm Hg. UV: M 240, 274 mp. (e 12,500, 9.130). IR: A J" 3431, 3271, 1275, 1686, 1661, 1616 cm Anal. Calcd. for C, -,H,,O NP: C, 54.04; H, 8.47; N, 4.20; P, 9.29. Found: C, 54.04; H, 8.63; N, 4.02; P, 9.64.

EXAMPLE 7 2-Diethylphosphono-2-bromoacetaldehyde Cyclohexylarnine Enamine To a solution of 5.00 g of diethylphosphonoacetaldehyde in 15.0 ml of anhydrous tetrahydrofuran, there is added dropwise 11.3 ml of 2.39N ethylmagnesium bromide-tetrahydrofuran solution within a period of 10 minutes under ice-cooling and stirring. After stirring for 30 minutes at room temperature, a solution of 2.02 g

of cyanogen bromide in 10.0 ml of anhydrous tetrahydrofuran is added dropwise within a period of 5 minutes under ice-cooling and then the reaction mixture is stirred for 2.5 hours at room temperature. The reaction mixture is poured into iceyield) having mp. 79 80 C. UV: 254 mp. (e

16,700). 1R2 1 3 2; 3371, 1635, 1242, 1056, 1031, 962 cm". Anal. calc'tffo'r c n ompsr: C, 42.36; H, 6.81; N, 4.12; P, 9.11; Br, 23.49. Found: C, 42.26; H, 2.06; N, 4.24; P, 9.84; Br, 23.62.

EXAMPLE 8 SB-Formylethylene-tifi-vinyl-B-nor-androstan-3a-ol To a mixture of 386 mg of 52.9 percent sodium hydride and 1.5 n11 of tetrahydrofuran, there is added a solution of 2.221 g of diethylphosphonoacetaldehyde cyclohexylamine enamine in 14.5 rnlv of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stirring is continued for 15 minutes. A solution of 1.19 g of SB-formyl-6B-vinyl-B-nor-androstan-3aol benzoate in 7.0 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept atroom temperature for 3.5 hours under stirring. Further, 300 mg of paraformaldehyde is added under ice-cooling and the reaction mixture is stirred for 30 minutes, then poured into ice-water, and extracted with ether-dichloromethane (4 1). The extract is washed with saturated sodium chloride aqueous solution and the solvent is evaporated to dryness to yield 2.686 g of residue. To a solution of this residue in 25 ml of benzene, there is added 1.7 g of oxalic acid and 75 ml of water. After, the solution is kept overnight at room temperature under stirring, the benzene layer is separated and the aqueous layer is extracted with ether-dichloromethane (6 1). The extract combined with the benzene layer is washed with saturated sodium chloride aqueous solution and then the solvent is evaporated to dryness to yield 1.658 g of residue. The residue is dissolved in ml of methanol and heated with 40 ml of 2N-potassium carbonate solution for 20 minutes under refluxing. The reaction mixture is concentrated under reduced pressure, poured into ice-water, and then extracted with ether-dichloromethane (4 1). The extract is evaporated under reduced pressure to yield 1.339 g of residue, which is passed through a column of 30 g of silica gel (containing 3 percent of water). Eluate with benzene-chloroform (1 1) is recrystallized from ether-pentane to afford 840 mg of 5B-formylethylene-6B-vinyl-B-norandrostan-Sa-ol (87 percent yield) having mp. 62 65 C.

To a mixture of 73 mg of 52.9 percent sodium hydride and 1.0 ml of tetrahydrofuran, there is enamine a solution of 398 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 2.0 ml of anhydrous tetrahydrofuran under icecooling and stirring, and then the Stirring is continued for 15 minutes. A solution of 500 mg of 17B-benzoyloxy-5a-androstan-3-one in 4.0 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 3.5 hours under stirring. The reaction mixture is poured into ice-water and the product is extracted with ether, washed with water and evaporated to dryness to yield 782 mg of residue. To a solution of this residue in 30 ml of benzene, there is added 800 mg of oxalic acid and 90 ml of water. After the solution is kept at room temperature for 17 hours under stirring, the benzene layer is separated and the aqueous layer is extracted with ether. The extract combined with the benzene layer is washed with water and evaporated to dryness to yield 551 mg of crystalline residue, which on recrystallization from ether affords 426 mg of 3-formylmethylcne-5a-androstan-17B-ol benzoate (80 percent yield) having mp. 157 158 c. UV: x 236 m;1.(e 21,700 1R: v g, 2783, 1683, 1632 cm". NMR: 8(CDC1 5.32 (doub iet), 10.30 (doublet) ppm. Anal. Calcd. for C i-1 C, 79.96; H, 8.63. Found: C, 79.49; H, 8.86.

EXAMPLE 3B-Hydroxy-17( 20)-5apregnen-21-al To a mixture of 59.7 mg of 52.9 percent sodium hydride and 1.0 ml of tetrahydrofuran, there is added a solution of 342 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 2.0 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stirring is continued for minutes. A solution of 164 mg of 3/3-tetrahydropyranyloxy-Sa-androstan-l7- one in 1.5 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 10 hours under stirring. The reaction mixture is poured into ice-water and the product is extracted with ether, washed with water and evaporated to dryness to yield 343 mg of residue. To a solution of this residue in 12 ml of benzene, there is added 445 mg of oxalic acid and 36 ml of water. After the solution is kept at room temperature for 22 hours under stirring, the benzene layer is separated and the aqueous layer is extracted with ether. The extract combined with the benzene layer is washed with 2N hydrochloric acid and then with water and evaporated to dryness to yield 208 mg of residue. The residue is dissolved in ml of 70 percent acetic acid and heated at 60 70 C. for minutes. The reaction mixture is' evaporated under reduced pressure, poured into ice-cooled saturated potassium carbonate aqueous solution and then extracted with ether. The extract is washed with water and evaporated to dryness to yield 132 mg of crude crystals, which on recrystallization from dichloromethane-ether afford 99 mg of 3B-hydroxy-17(20)-5a-pregnen-21-al (71.2 percent yield) having mp. 176 180 C. UV: M 245 my. (5 14,500. IR: vgg 2758, 1669, 1640, 1610 cm. NMR: 8(CDCl 5.69 (multiplet), 9.78 (doublet) ppm. Anal. Calcd. for 0 ,11, 0 C, 79.70; H, 10.19. Found: C, 79.07; H, 10.12.

EXAMPLE 1 l Sa-Formylethylenepregnane-3,20-dione To a mixture of 105 mg 52.9 percent sodium hydride and 0.5 ml of tetrahydrofuran, there is added a solution of 605 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 1.0 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stirring is continued for 15 minutes. Then a soluu'on of 100 mg of 3,3:20,20-bisethylcnedioxy-Sa-formylpregnane in 2.0 ml of anhydrous tetrahydrofuran is added and the resulting solution is refluxed for 9 hours. Thereafter, according to the same procedure as Example 3, the reaction produce is treated with 840 mg of oxalic acid and 30 ml of water and then with 30 m1 of 70 percent acetic acid. Thus resulting produce is crystallized from ether to afford 71 mg of 5a-formylethylenepregnane-3,20-dione (82.7 percent yield) having mp. 140 144 C. UV: M 220.5 mp. (5

13,850). m; 75%,? 2736, 1695, 1623 cm- NMR:

6(CDCl 6.13 (quartet, J 16 cps), 7.27 (doublet, J 16 cps), 9.52 (doublet) ppm. Anal. Calcd. for C H O C, 77.80; H, 9.25. Found: 0, 77.80; H, 9.25.

EXAMPLE l2 l7( 20)-5a-Pregnen-21-al To a mixture of 99 mg of 52.9 percent sodium hydride and 1.4 ml of tetrahydrofuran, there is added a solution of 568 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 2.2 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stirring is continued for 15 minutes. Then, a solution of 200 mg of 5a-androstan-17-one in 1.4 ml of anhydrous tetrahydrofuran is added and the resulting solution is is treated as usual manner, and the product is dissolved in ml of benzene. The solution, to which is added 1.05 g of oxalic acid and 105 m1 of water, is kept at room temperature for 13 hours under stirring. Thereafter, the product worked up as usual manner is crystallized from ether to afford 162 mg of 17(20)-5a-pregnen-21-al (74.0 percent yield) having mp. 150 152 (3. UV; x 245 mp. (5 16,500). IR: .353 2758, 1670, 1640, 1610 cm. NMR: 8(CDCl 5.73 (multiplet), 9.87 (doublet) ppm. Anal. Calcd. for C H O: C, 83.94; H, 10.73. FoundfC, 83.60; H, 10.78.

EXAMPLE 13 Cinnamic Aldehyde To a mixture of 653 mg of 52.9 percent sodium hydride and 6.5 ml of tetrahydrofuran, there is added a solution of 3.76 g of diethylphosphonoacetaldehyde cyclohexylamine enamine in 20 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stir-ring is continued for 15 minutes. Then, a solution of 1.27 g of benzaldehyde in 13 ml of anhydrous tetrahydrofuran is added and the resulting solution is kept at room temperature for 2 hours under stirring. Thereafter, the product worked up as usual manner is purified by vacuum distillation to afford 1.22 g of cinnamic aldehyde (77.2 percent yield) having bp. 78 C./1.0 mm Hg. UV: M 287 my. (6 22,400). 1R: 72,21. 1692, 1630 cm.

Semicarbazone: mp. 106 209 C. UV: h 312 my. (6 34,900). Anal. Calcd. for C H ON c, 63.47; H, 5.86; N, 22.21. Found: C, 63.42; H, 5.85; N, 22.44.

EXAMPLE 14 3,3-Ethylenedioxy-1IB-hydroxy-S,17(20)-pregnadien-2l-al To a mixture of 39 mg of 52.9 percent sodium hydride and 0.5 ml of tetrahydrofuran, there is added a solution of 226 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 1.5 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stirring is continued for 15 minutes. Then, a solution of 100 mg of 3,3-ethylenedioxy-1IB-hydroxy-S-androsten-17-one in 1.0 ml of anhydrous tetrahydrofuran is added and the resulting solution is kept at room temperature for 19 hours under stirring. The reaction mixture is poured into ice-water, extracted with dichloromethane, washed with water, dried over anhydrous sodium sulfate and evaporated to dryness to yield 234 mg of residue. The residue is dissolved in a mixture of dichloromethane and tetrahydrofuran (5 l) and treated with a buffer solution (pH 4.1), prepared from 10 ml of 0.385M tartaric acid and 10 ml of 0.385M sodium hydroxide, at room temperature for 38 hours under stirring. The reaction mixture is poured into water, extracted with dichloromethane, washed with water, dried over anhydrous sodium sulfate and evaporated to dryness to yield 149 mg of residue, which is passed through a column of 3 g of alumina. Eluate with benzene or benzenedichloromethane (l 1) is ,7 recrystallized from dichloromethane-ether to afford 69 mg of 0 3,3-ethylenedioxy1 lB-hydroxy-S,17(20)-pregnadien-21-al having mp. 224 226 C. Anal. Calcd. for C, H O C, 74.16; H, 8.66. Found: C, 73.94; H, 8.63.

EXAMPLE 15 Cyclohexylidene Acetaldehyde According to the same procedure as the above examples, cyclohexanone is subjected to reaction with diethylphosphonoacetaldehyde cyclohexylamine enamine to kept at room temperature for 10 hours. The reaction mixture yield cyclohexylidene acetaldehyde having bp. 88 89 C 16 mm Hg. uv. x 240 my. (6 15,200). IR: #28; 1682 cm". NMR: 8(CDCl 6.86, 9.93 ppm. From the signals of IR and NMR spectra, the contamination of a small quantity of deconjugated aldehyde, i.e. cyclohexenyl acetaldehyde, is recognized.

Thus resulting oily cyclohexylidene acetaldehyde is then subjected to reaction with sodium acetate and semicarbazidehydrochloride in ethanol to yield the semicarbazone (86.4 percent yield from cyclohexanone) having mp. 212 213 C. UV: A 273.5 my. 34.000).

EXAMPLE 16 2-Cyclohexylidenepropionaldehyde To a mixture of 82 mg of 52.9 percent sodium hydride and 0.5 ml of tetrahydrofuran, there is added a solution of 497 mg of 2-diethylphosphonopropionaldehyde cyclohexylamine enamine in 1.0 ml of anhydrous tetrahydrofuran under icecooling and stirring. The stirring is continued for minutes and a solution of 147 mg of cyclohexanone in 1.0 ml of anhydrous tetrahydrofuran is then added. The reaction mixture is kept at room temperature for 5.5 hours under stirring and then poured into ice-water. The product is extracted with ether and washed with saturated sodium chloride aqueous solution, then the basic portion extracted with 20 percent tartan'c acid. To the tartaric acid layer is added potassium carbonate under ice-cooling to be slightly basic. The precipitated product is extracted with ether, washed with saturated sodium chloride aqueous solution and evaporated to dryness to yield crude crystals, which on recrystallization from ether-pentane afford the intermediary Schiff-base having mp. 77 78 C. UV: A 246.5 m (5 24,200 IR: .5 3, 2664, 1632, 1614 cm". Anal. Calcd. for C,,,H N: C, 82.13; H, 11.49; N, 6.38. Found: C, 82.00, H, 11.69; N, 6.15.

To a solution of this intermediary Schiff-base in 23 ml of benzene, there is added 718 mg of oxalic acid and 70 ml of water and the solution is then refluxed for 1 hour under nitrogen atmosphere. After cooling, the benzene layer is separated and the aqueous layer is extracted with ether. The extract combined with the benzene layer is washed with 2N sodium carbonate and saturated sodium chloride aqueous solution and evaporated to dryness to yield 152 mg of residue. The residue is purified by vacuum distillation to afford 129 mg of 2-cyclohexylidenepropionaldehyde (62.6 percent yield from cyclohexanone) having bp. 60 C./0.10 0.15 mm Hg (bath temperature). On the other hand, the residue obtained by the reaction with oxalic acid, without distilling, may be immediately converted to the 2,4-dinitrophenylhydrazone as crystals having mp. 187 190 C. in 66.2 percent yield from cyclohexanone.

2,4-Dinitrophenylhydrazone: recrystallized from dichloromethane-ethanol. UV: k f 223 my. (6 13,400), 259 14,750 295 (8,900), 389 (25,600). 1R: ,ggg 3292, 1619, 1596, 1334, 1137, 834 cm". Anal. Calcd. tor C ,,H O N C, 56.59; H, 5.70; N, 17.60. Found: C, 56.50; H, 5.70; N, 17.40.

EXAMPLE 17 2-Cyclohexylidene'3-phenylpropionaldehyde To'a mixture of 187 mg of 52.9 percent sodium hydride and 1.5 ml of tetrahydrofuran, there is added a solution of 2.905 g of 3-phenyl-2-diethylphosphonopropionaldehyde cyclohexylamine enamine in 4.0 ml of anhydrous tetrahydrofuran under ice-cooling and stirring. The stirring is continued for 15 minutes and a solution of 405 g of cyclohexanone in 4.0 ml of anhydrous tetrahydrofuran is then added. The reaction mixture is refluxed for 3 hours. After cooling, the reaction mixture is poured into ice-water, extracted with ether, washed with saturated sodium chloride aqueous solution and evaporated to dryness to yield 2.496 g of residue. A portion (1.704 g) of this residue is dissolved in 50 m1 of benzene and treated, according to the same procedure as Example 9, with 3.63 g of oxalic acid and 146 ml of water to yield 1.271 g of residue. The residue is passed through a column of silica gel (Woelm: containing 10 percent of water) and eluted with benzene or benzene-dichloromethane (1 1) to afford 408 mg of cyclohexylidene-3-phenylpropionaldehyde (67.3 percent yield), which is identified as 2,4-dinitrophenylhydrazone having mp. 162 174 C. (recrystallized from dichloromethaneethanol). IR: v,,,,,,'' 3294, 1613, 1594, 1515, 1326, 1134, 835 cm". Anal. Calcd. for C H O N C, 63.94; H, 5.62; N, 14.21. Found: C, 63.64; H, 5.66; N, 14.50.

EXAMPLE 18 3,3-Ethylenedioxy-l 1-oxo-5,1 7( 20 )-pregnadien-2 l-al To a mixture of 26.9 mg of 52.9 percent sodium hydride and 0.4 ml of anhydrous tetrahydrofuran, there is added a solution of 155 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 1.0 ml of anhydrous tetrahydrofuran under icecooling and stirring. The stirring is continued for 15 minutes and a solution of 68 mg of 3,3-ethylenedioxy-S-androstene- 11,17-dione in 0.7 ml of anhydrous tetrahydrofuran is then added. The reaction mixture is kept at room temperature for 21 hours under stirring and then poured into ice-water. The produce is extracted with ether, washed with water, dried over anhydrous sodium sulfate and evaporated to dryness to yield 171 mg of residue. The residue is dissolved in 3.0 ml of benzene and then 1.088 g of sodium acetate, 480 g of acetic acid and 3.0 ml of water are added. The resulting mixture is kept at room temperature for 21 hours under stirring and the product is extracted with ether, washed with water and evaporated to dryness to yield 126 mg of residue, which is passed through a column of 4 g of alumina. Eluate with benzene or benzene-dichloromethane is recrystallized from dichloromethane-ether to afford 53.2 mg of 3,3-ethylenedioxy-ll-oxo5,17(20)-pregr|adien-21-al (72.8 percent yield) having mp. 208 212 C. [01],, 47.6 I 2.2 (C 0.397: chloroform). Anal. Calcd. for C, H O,: C, 74.56; H, 8.16. Found: C, 74.29; H, 8.14.

EXAMPLE 19 1-Formylmethylene-6-methoxytetraline To a mixture of 155 mg of 52.9 percent sodium hydride and 1.0 ml of tetrahydrofuran, there is added a solution of 892 mg of diethylphosphonoacetaldehyde cyclohexylamine enamine in 2.0 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and then stirring is continued for 15 minutes. A solu tion of 200 mg of 6-methoxy-a-tetralone in 2.0 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 6.5 hours under stirring. The reaction mixture is then poured into ice-water, extracted with ether, washed with water, dried over anhydrous sodium sulfate and then evaporated to dryness to yield 790 mg of syrupy residue. The residue is dissolved in 29 ml of benzene and then 868 mg of oxalic acid and 86 ml of water are added. The mixture is kept at room temperature for 13 hours under stirring and then extracted with ether. Ether extract is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness to yield 114 mg of crystalline residue, which on recrystallization from dichloromethane-ether affords 34 mg of 1-formylmethylene-6-methoxytetraline (31 percent yield) having mp. 89 90 C. IR: m 2774, 1656, 1610, 1591, 1151 cm". Anal. Calcd. for C I- 0 2 C 77.20; H, 6.98. Found: C, 76.85; H, 7.01.

EXAMPLE 20 According to the similar procedure as described above, a- (2,6,6u'imethyl-l-cyclohexenyl)-acetaldehyde is converted to a-(2,6,6-trimethyl-1-cyclohexenyl)-a-methylcrotonic aldehyde (bp. 99 103 C./0.5 mm Hg; identified as semicarbazone: mp. 157 C.), cinnamalacetaldehyde to 7- phenylheptatrienal (mp. 114 116 C), and 2,7 dimethylocta-2,6dien-4-yne-1,8-dial to 4,9-dimethyldodeca-2,4,8,10- tetraen-6-yne-l,12-dial (mp. 162 163 C.), respectively.

EXAMPLE 2 1 Cinnamic Aldehyde To a mixture of 590 mg of 52.9 percent sodium hydride and 6.0 ml of tetrahydrofuran, there is added a solution of 3.80 g of ethyl-Z-cyclohexylaminovinyl phenylphosphinate in 20 ml of anhydrous tetrahydrofuran and then the mixture is stirred for 20 minutes. A solution of 1.06 g of benzaldehyde in 11 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 4 hours under stirring. The reaction mixture is then added into ice-water, extracted with ether, washed with water, dried over anhydrous sodium sulfate and evaporated to yield 3.16 g of residue. To a solution of this residue in 100 ml of benzene, there is added 1.0 g of oxalic acid and 300 ml of water and the solution is then stirred for 14 hours at room temperature. Benzene layer is separated and the aqueous layer extracted with ether. The extract combined with the benzene layer is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness to yield 1.37 g of residue, which on purification by vacuum distillation afiords 0.96 g of cinnamic aldehyde (72.5 percent yield) having bp. 78 C./ 1.0 M mm Hg.

EXAMPLE 22 a-Methylcinnamic Aldehyde To a mixture of 318 mg of 52.9 percent sodium hydride and 3.0 ml of tetrahydrofuran, there is added a solution of 2.15 g of ethyl-(2-cyclohexylamino-1-methyl)vinyl phenylphosphinate in 12 ml of anhydrous tetrahydrofuran, and then the mixture is stirred for 20 minutes. A solution of 530 mg of benzaldehyde in 5.0 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 20 hours under stirring. According to the same procedure as Example 21, the reaction mixture is treated and then hydrolyzed with oxalic acid. The resulting product is purified by vacuum distillation to afford 469 mg of a-methylcinnamic aldehyde (64.3 percent yield) having bp. 131 132 C./1.6 mm Hg, identified as semicarbazone: mp. 206 208 C. Anal. Calcd. for c u oN C, 65.00; H, 6.45; N, 20.68. Found: C, 65.13; H, 6.29; N, 20.51.

EXAMPLE 23 B-Phenylcynnamic Aldehyde To a mixture of 318 mg of 52.9 percent sodium hydride and 3.0 ml of tetrahydrofuran, there is added a solution of 2.05 g of ethyl-2-cyclohexylaminovinyl phenylphosphinate in 11 ml of anhydrous tetrahydrofuran, and then the mixture is stirred for 20 minutes. A solution of 911 mg of benzophenone in 9.0 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 8 hours under stirring. According to the same procedure as Example 21, the reaction mixture is treated and then hydrolyzed with oxalic acid. The resulting product is recrystallized from petroleum ether to afiord 655 mg of B-phenylcynnamic aldehyde (63.0 percent vield) as yellowish crystals having mp. 440 455 C. IR: .359 2750, 165516001580, 123s, 115s, 1135, 870 cm. Anal. Calcd. for C H O: C, 86.51; H, 5.81. Found: C, 86.66; H, 5.90. Semicarbazone: mp. 214 215 C.

EXAMPLE 24 2-Cyclohexylidenepropionaldehyde To a mixture of 218 mg of 52.9 percent sodium hydride and 2.0 ml of tetrahydrofuran, there is added a solution of 1.23 g of ethyl-(Z-cyclohexylamino-l-methyl)vinyl phenylphosphinate in 5 ml of anhydrous tetrahydrofuran, and the mixture stirred for 20 minutes. A solution of 294 mg of cyclohexanone in 3.0 ml of anhydrous tetrahydrofuran is then added and the resulting solution is kept at room temperature for 7 hours under stirring. The reaction mixture is poured into ice-water, extracted with ether, washed with saturated sodium chloride aqueous solution and further extracted with 20 percent tartaric acid solution to remove the basic portion. The tartaric acid layer is treated with potassium carbonate under ice-cooling to make slightly basic. The product is then extracted with ether, washed with saturated sodium chloride aqueous solution and evaporated to dryness to yield crude crystals, which on recrystallization from ether-pentane afford the Schiif-base intermediate, having mp. 77 78 C, which is identical with an authentic specimen prepared in Example 16.

According to the same procedure as Example 16, this intermediate is hydrolyzed with oxalic acid in benzene and the product is purified by vacuum distillation to afford 324 mg of 2-cyclohexylidenepropionaldehyde (58.8 percent yield) 14 which is identified as 2,4-dinitrophenylhydrazone (mp. 187 190 C.

EXAMPLE 25 3-Formylmethylene-Sa-androstan-17B-ol Benzoate To a mixture of 59 mg of 52.9 percent sodium hydride and 1 ml of tetrahydrofuran, there is added a solution of 380 mg of ethyl-2-cyclohexylaminovinyl phenylphosphinate in 2.0 ml of anhydrous tetrahydrofuran, and the mixture is then stirred for 20 minutes. A solution of 395 mg of l7fi-benzoyloxy-5a-androstan-B-one in 3.0 ml of anhydrous tetrahydrofuran is added and the resulting solution is kept at room temperature for 6.5 hours under stirring. According to the same procedure as Example 21, the reaction mixture is treated and then hydrolyzed with oxalic acid. The resulting product is recrystallized from ether to afford 298 mg of 3-formylmethylene-5a-androstan- 17,301 benzoate (71.0 percent yield), having mp. 157 158 C, which is identical with an authentic specimen prepared in Example 9.

.ELE 26 17(20)-5a-pregnen-2l-al Reaction of 5a-androstan-17-one with ethyl-2-cyclohexylaminovinyl phenylphosphinate, according to the same procedure as Example 25, afiords l7(20)-5a-pregnen-2l-al (recrystallized from ether) having mp. 150 152 C. in about percent yield, which is identical with an authentic specimen prepared in Example 12.

EXAMPLE 27 5a-Formylethylenepregnane-3,20-dione According to the same procedure as Example 25, 3,320,20- bisethylenedioxy-Sa-formylpregnane is subjected to reaction with ethyl-2-cyclohexylaminovinyl phenylphosphinate. Hydrolysis with oxalic acid and subsequent deketallization with 70 percent acetic acid at 60 -70 C. afford Sa-formylethylenepregnane-3,20-dione having mp. 140 144 C. in about percent yield, which is identical with an authentic sepcirnen prepared in Example 11.

EXAMPLE 28 2-Cyclohexylidene-3-phenylpropionaldehyde To a mixture of 364 mg of 52.9 percent sodium hydride and 3.5 ml of tetrahydrofuran, there is added a solution of 3.07 g of ethyl-(1-benzyl-2-cyclohexylamino)vinyl phenylphosphinate in 4.0 ml of anhydrous tetrahydrofuran under ice-cooling and stirring, and the mixture is then stirred for 20 minutes. A solution of 393 mg of cyclohexanone in 4.0 ml of anhydrous tetrahydrofuran is added and the resulting solution is refluxed for 4 hours. After cooling, the reaction mixture is poured into ice-water, extracted with ether, then treated in the same manner as Example 21, and then further hydrolyzed with oxalic acid. The product is purified by passing through a column of silica gel to afford 411 mg of 2-cyclohexylidene-3-phenylpropionaldehyde (48.1 percent yield), which is converted to 2,4-dinitrophenylhydrazone identical with an authentic specimen prepared in Example 17.

EXAMPLE 29 3,3Ethylenedioxy-1 l-oxo-5,17( 27 )-pregnadien-2 l-al To a mixture of 136 mg of 52.9 percent sodium hydride and 1.0 ml of tetrahydrofuran, there is added a solution of 880 mg of ethyl-Z-cyclohexylaminovinyl phenylphosphinate in 7 ml of anhydrous tetrahydrofuran, and the mixture is then stirred for 20 minutes under ice-cooling. A soluu'on of 340 mg of 3,3-

' ethylenedioxy-S-androstene1 1,17-dione in 3 ml of anhydrous tetrahydrofuran is added and the resulting solution is kept at 3,3-ethylenedioxy-11-oxo-5,l7(20)-pregnadien-2l-al 208 room temperature for 24 hours under stirring. The reaction mixture is poured into ice-water, extracted with ether, washed with water, dried over anhydrous sodium sulfate and evaporated to dryness to yield 930 mg of residue. To a solution of this residue in 16 ml of benzene, there is added 5.3 g of sodium acetate, 2.31 g of acetic acid and 16 ml of water, and

wherein R is a lower alkyl group, R is a member selected from the group consisting of R 0, a lower alkyl. group, an aralkyl group of seven to eight carbon atoms and an aryl group of six to seven carbon atoms, R is a member selected from the group consisting of an acyclic or cyclic alkyl group of one to six carbon atoms and an aryl group of six to seven carbon atoms, and R is a member selected from the group consisting of a hydrogen atom, a lower alkyl group, an aralkyl group of seven to eight carbon atoms, and a halogen atom.

2. A compound according to clam 1, namely dirnethylphosphonoacetaldehyde t-butylamine enamine,

3. A compound according to claim 1, namely dimethylphosphonoacetaldehyde cyclohexylamine enamine.

4. A compound according to claim 1, namely dimethylphosphonoacetoldehyde i-propylamine enamine.

5. A compound according to claim 1, namely diethylphosphonoacetaldehyde cyclohexylamine enamine.

6. A compound according to 1, namely 2- diethylphosphonopropionaldehyde t-butylamine enamine.

7. A compound according to claim 1, namely 2- diethylphosphonopropionaldehyde cycloheylamine enamine.

8. A compound according to claim 1, namely 2- diethylphosphono-n-butyaldehyde cyclohexylamine enamine.

9. A compound according to claim 1, namely 2- diethylphosphono-3-phenylpropionaldehyde cyclohexylamine diethylphosphono-2-bromoacetaldehyde enamine.

10. A compound according to claim 1, namely 2- cyclohexylamine enamine.

11. A compound according to claim 1, namely ethyl-2- cyclohexylaminovinyl phenylphosphinate.

12. A compound according to claim 1, namely ethyl-lmethyl-2-cyclohexylaminovinyl phenylphosphinate.

13. A compound according to claim 1, namely ethyl-ethyl- 2-cyclohexylaminovinyl phenylphosphinate.

14. A compound according to claim 1, namely ethyl-(lbenzyl-2-cyclohexylamino )vinyl phenylphosphinate.

15. A compound according to claim 1, namely ethyl-2-t-butylarninovinyl phenylphosphinate. 

2. A compound according to clam 1, namely dimethylphosphonoacetaldehyde t-butylamine enamine.
 3. A compound according to claim 1, namely dimethylphosphonoacetaldehyde cyclohexylamine enamine.
 4. A compound according to claim 1, namely dimethylphosphonoacetoldehyde i-propylamine enamine.
 5. A compound according to claim 1, namely diethylphosphonoacetaldehyde cyclohexylamine enamine.
 6. A compound according to claim 1, namely 2-diethylphosphonopropionaldehyde t-butylamine enamine.
 7. A compound according to claim 1, namely 2-diethylphosphonopropionaldehyde cycloheylamine enamine.
 8. A compound according to claim 1, namely 2-diethylphosphono-n-butyaldehyde cyclohexylamine enamine.
 9. A compound according to claim 1, namely 2-diethylphosphono-3-phenylpropionaldehyde cyclohexylamine enamine.
 10. A compound according to claim 1, namely 2-diethylphospHono-2-bromoacetaldehyde cyclohexylamine enamine.
 11. A compound according to claim 1, namely ethyl-2-cyclohexylaminovinyl phenylphosphinate.
 12. A compound according to claim 1, namely ethyl-1-methyl-2-cyclohexylaminovinyl phenylphosphinate.
 13. A compound according to claim 1, namely ethyl-ethyl-2-cyclohexylaminovinyl phenylphosphinate.
 14. A compound according to claim 1, namely ethyl-(1-benzyl-2-cyclohexylamino)vinyl phenylphosphinate.
 15. A compound according to claim 1, namely ethyl-2-t-butylaminovinyl phenylphosphinate. 